Drug-delivery systems with the capability to respond to a given stimulus can dramatically improve therapeutic efficacy. The development of such systems currently relies on responsive polymeric materials that need to be chosen specifically for each application. However, this strategy is limited by the availability of such polymeric systems and thus every new application is a new challenge. One different approach in smart drug-delivery systems has achieved on-demand drug delivery by employing molecular machines as nanovalves.[1] Redox activation;[2] competitive binding;[3] pH,[4] temperature-[5] or light-initiated,[6] and biological [7] triggers have been used for controlled release. In this report, we demonstrate that the molecular recognition capacity of aptamers can be used to design reversible, stimuli-responsive polymeric hybrid systems, such that any polymeric nanocarrier can be functionalized to respond to potentially any kind of trigger molecule. The incorporation of aptamers as nanovalves would bring about a generic system in drug delivery, since aptamers can be selected to a wide variety of targets from ions to whole cells in vitro. Aptamers are nucleic acids with biorecognition properties that can go along with a switching of their structure.[8] These two properties of aptamers can be combined to improve the performance of drug-delivery nanocarriers in two aspects: 1) better control of the release kinetics and 2) the range of potential trigger stimuli can be extended. Nevertheless, the potential of aptamers for creating stimulus-responsive materials through pore-gating has been limited to only two recent reports. Abelow et al.[9] modified 20 and 65 nm radii glass nanopores with cocaine aptamers in order to control ion transport. Zhu et al.[10] showed that controlled release can be achieved in mesoporous silica nanoparticles with a snaptop design using ATP-binding aptamers attached to gold nanoparticles as a responsive molecular gate. Herein we report on a switchable nanovalve directly using an ATP-binding aptamer sequence (Figure 1) that was covalently attached onto the surface of nanoparticles. This system was found to be highly reversible, which means that partial delivery of drug molecules can be controlled better instead of a sudden release as is the case in snap-top designs. Our drug-delivery system was centred on the conversion of an aptamer sequence into a molecular-beacon-type hair-[a] Prof. VC Özalp, Dr. T. Schäfer Institute for Polymer Materials (POLYMAT) University of the Basque Country (UPV/EHU) Avda. De Tolosa 72, 20018 Donostia-San Sebastiµn (Spain) Fax:(+ 34) 943-01-7065